The occurrence of degenerative diseases increases with aging. Degeneration of the central nervous system (CNS) leaves patients devastated with presenile or senile forms of dementia. While the etiologies of most forms of dementia remain obscure, the number of demented patients is progressively increasing as the proportion of our population comprised of older people continues to grow. Toward gaining a better understanding of these age-dependent degenerative changes, we plan to focus our research on viral degenerations of the CNS. The dramatic degeneration of the CNS produced by the scrapie and Creutzfeldt-Jakob Disease (CJD) slow transmissible agents make them excellent models for studying degenerative diseases. In this program application we propose purification and characterization studies of the scrapie agent, studies on the biological and biochemical properties of the CJD agent, development of tissue culture systems for propagation of the CJD agent and studies of the pathogenesis and ultrastructural morphology of experimental CJD. Our research efforts will be of significance in the diagnosis, cure and possibly treatment of older patients with dementia as well as in defining the unusual properties of a novel class of microorganisms, having incubation periods measured in decades and capable of causing profound degeneration of the CNS.